A quick guide on Transition State in Organic Reactions

What is a transition state?

A chemical reaction’s transition state is a specific position on the reaction coordinate. Using this reaction coordinate, it is defined as the state with the largest potential energy.

Transition state theory

Transition state theory (TST) provides a simple and useful way to understand and determine the rate coefficients of chemical reactions. It was first proposed by Eyring and Evans-Polanyiin 1935.

The reaction rates of elementary chemical reactions are explained by transition state theory (TST). The theory assumes that reactants and activated transition state complexes are in a special type of chemical equilibrium (quasi-equilibrium).

TST is primarily used to gain a qualitative understanding of chemical reactions. Because calculating absolute reaction rates necessitates precise knowledge of potential energy surfaces, TST has had less success in its original goal of calculating absolute reaction rate constants. Examining activated complexes near the saddle point of a potential energy surface can be used to investigate reaction rates. It is unimportant to know how these complexes are formed. The transition state refers to the saddle point itself.

The activated complexes and the reactant molecules are in a special equilibrium (quasi-equilibrium).

The activated complexes can be converted into products, and the rate of conversion can be calculated using kinetic theory.

Limitations

TST has provided a conceptual foundation for researchers to understand how chemical reactions occur. Despite its broad applicability, the theory has limitations.

The assumption that atomic nuclei behave according to classical mechanics also underpins transition state theory. It is assumed that the reaction will not occur unless atoms or molecules collide with enough energy to form the transition structure.

At high temperatures, the transition state theory fails for some reactions. The reaction system will pass over the lowest energy saddle point on the potential energy surface, according to the theory. While this description holds true for reactions occurring at low temperatures, at high temperatures, molecules populate higher energy vibrational modes, making their motion more complex and potentially resulting in collisions, leading to states that are far from the lowest energy saddle point.

Transition state enzyme

Enzymes stabilise the structure of the transition state by binding substrates to their active sites. As a result, the free energy of the transition state decreases, lowering the rate of the chemical reaction. Enzymes, on the other hand, have no effect on the Gibbs free energy of a chemical reaction. That is, neither the free energy of the products nor the free energy of the reactants is changed. This means that, while the time it takes to reach equilibrium in a catalysed reaction decreases, the concentrations of products and reactants do not change once equilibrium is reached. We conclude that enzymes reduce reaction rate by lowering the Gibbs free energy of activation, but they have no effect on the reaction’s actual equilibrium.

When compared to uncatalysed chemistry under the same reaction conditions, enzymes catalyse chemical reactions at incredible speeds. Each catalytic event necessitates at least three, and frequently more, steps, all of which occur in the milliseconds that are typical of enzymatic reactions. According to transition state theory, the most important step, the transition state, takes up the smallest portion of the catalytic cycle. The transition state was originally defined as a distinct species in the reaction coordinate that determined the absolute reaction rate in the original proposals of absolute reaction rate theory for chemical reactions.

It is now widely accepted that enzymes function to stabilize transition states between reactants and products and that they should bind strongly to any inhibitor that comes their way, resembling a transition state in this way. Because substrates and products frequently participate in multiple enzyme-catalysed reactions, but the transition state is usually unique to one enzyme, such an inhibitor is usually specific for that enzyme. The discovery of a large number of transition state inhibitors lends credence to the transition state stabilisation hypothesis for enzymatic catalysis.

Transition state symbol

A chemical reaction’s transition state is a specific configuration along the reaction coordinate. It’s the state that corresponds to the reaction coordinate with the highest potential energy. It is frequently denoted by the double dagger symbol.

double dagger ‡ symbol

Conclusion

The Arrhenius rate law was widely used to determine reaction barrier energies prior to the development of TST. The Arrhenius equation is based on empirical data and ignores any mechanistic considerations, such as whether one or more reactive intermediates are involved in the reaction. To fully comprehend the two parameters associated with this law, the pre-exponential factor (A) and the activation energy, more research was required.